The potential role of retinoic acid receptor α on glomerulosclerosis in rats and podocytes injury is associated with the induction of MMP2 and MMP9.

Retinoic acid receptor α (RARα) plays a crucial role in kidney disease. However, the underlying mechanisms in glomerulosclerosis (GS) is still not clear. The roles of RARα in an adriamycin (ADR)-induced GS rat model and in ADR-induced podocyte injury in vitro were investigated. RARα was over-expressed in GS rats, and serum, urine and kidney samples were collected to detect the induction of the expression of the receptor. RARα expression was inhibited and/or over-expressed in cultured podocytes following injury, as demonstrated by morphometric assays, cell toxicity, and matrix metalloproteinase (MMP) enzymatic activity. RARα displayed a renoprotective role in GS rats, resulting in a lower GS index, podocyte foot process fusion, and proteinuria, reduced serum creatinine and blood urea nitrogen. Further experiments indicated that RARα inhibited the accumulation of TGF-β1, α-smooth muscle actin, collagen IV, and fibronectin, while it induced MMP2 and MMP9 excessive expression in podocytes in vitro. RARα improved the renal function and attenuated the progression of GS that was associated with the over-expression of MMP2 and MMP9.